In our pilot work we have shown that a group of children fitting RDC criteria for major depressive disorder in adults, can be identified by structured interview. We propose to study in these children psychobiological parameters which are known to be relevant to adult depressive illnesses. This will be done in order to: 1) Validate the diagnosis of prepubertal depressive illness and 2) Establish its relationship to adult depressive illnesses. In order to meet this objective we will carry out three interrelated studies: Study I is a double blind placebo controlled study of imipramine, coupled with studies of drug bioavailability. Study II is a genetic family study, comparing the prevalence of affective disorder and alcoholism in families of probands and controls. Study III is a long-term follow up of index children and controls. In an interlocking application being submitted simultaneously three other parameters are to be studied: sleep, endocrine and MHPG excretion.